Although a variety of drugs have been detected in sweat, little information is available on the characteristics of drug excretion in sweat under controlled dosing conditions. A series of clinical studies were designed to determine the identity, concentration, time course, dose dependency and variability of drug and metabolite excretion in sweat following administration of single doses of cocaine and heroin to human subjects. Sweat was collected by means of a sweat patch that could be worn for a period of several days to several weeks at a time resulting in accumulation of drug in the patch. Sweat patches were removed at specified times and frozen until analyzed by gas chromatography/mass spectrometry. Cocaine and heroin were the major analytes excreted in sweat following their administration. Smaller amounts of cocaine metabolites were also detected following cocaine administration. 6- Acetylmorphine appeared rapidly after heroin administration and continued to increase while heroin content decreased, suggesting that heroin was undergoing hydrolysis in the sweat patch. Cocaine appeared in sweat within 1-2 hrs and peaked within 24 hrs in an apparent dose dependent manner. Analysis of duplicate adjacent patches from individual subjects who had been administered cocaine provided similar quantitative results suggesting that intra-subject variability was relatively low, whereas inter-subject variability was high. These observations regarding the excretion of cocaine and heroin analytes in sweat have important forensic implications to other fields such as hair analysis. Sweat excretion could be an important mechanism by which drugs enter hair. These data also suggest that the sweat patch could serve as a useful monitoring device in surveillance of individuals in treatment and probation programs.